Journal
ACS NANO
Volume 5, Issue 11, Pages 8690-8699Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn202597c
Keywords
capsid protein; siRNA delivery; nanocarrier; gene silencing; recombinant proteins
Categories
Funding
- Converging Research Center through the Ministry of Education, Science and Technology [2010K001205]
- National Research Foundation of Korea (NRF)
- Korea government (MEST) [2010-0029206]
- National Research Foundation of Korea [2010-0029206] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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For the efficient cytoplasmic delivery of siRNA, we designed a chimeric capsid protein composed of a capsid shell, integrin targeting peptide, and p19 RNA binding protein. This recombinant protein assembled into a macromolecular container-like structure with capsid shell and provided a nanocarrier for siRNA delivery. Our capsid nanocarriers had dual affinity both for siRNA within the interior and Integin receptors on the exterior, and the capsid shell structure allowed the encapsulated siRNAs to be protected from the external nucleases, leading to the enhanced stability of siRNA in serum conditions. The capsid nanocarriers could complex with siRNA in a size-dependent and sequence-independent manner and showed the pH-dependent complexing/dissocation behaviors with siRNA. Moreover, RGD peptides on the exterior surface of the capsid shell enabled the capsid nanocarriers to deliver siRNA into the cytosol of the target cells. Here, we demonstrated the superior efficiency of our siRNA/capsid nanocarrier complexes in RFP gene silencing, compared to untreated cells. These results provide an alternative approach to enhancing the stability of siRNA as well as to achieving targeted siRNA delivery.
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